Good grief: cell to cell mitochondrial migration!
http://www.pnas.org/...g&pmid=16432190
Posted 31 October 2006 - 09:16 AM
Posted 02 November 2006 - 10:40 PM
Posted 03 November 2006 - 06:04 AM
Posted 04 November 2006 - 12:52 PM
Posted 06 December 2006 - 09:41 PM
Posted 08 December 2006 - 01:48 PM
Posted 08 December 2006 - 03:18 PM
That is what mitochondria do physiologically: They import electron-carrying molecules like NADH and FADH2 and use the electrons to reduce oxygen to water.
"The environment" of the mitochondria is the cytosole. They cannot be engineered to take up extracellular electrons; the border between the extracellular space and the cell is the plasma membrane that actually exportselectrons.
Posted 12 December 2006 - 05:09 PM
Posted 12 December 2006 - 05:39 PM
how do you explain the lack of increase in maximum lifespan even at very high doses of applied antioxidants?
Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors.
* Campisi J.
Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA. jcampisi@lbl.gov
Cells from organisms with renewable tissues can permanently withdraw from the cell cycle in response to diverse stress, including dysfunctional telomeres, DNA damage, strong mitogenic signals, and disrupted chromatin. This response, termed cellular senescence, is controlled by the p53 and RB tumor suppressor proteins and constitutes a potent anticancer mechanism. Nonetheless, senescent cells acquire phenotypic changes that may contribute to aging and certain age-related diseases, including late-life cancer. Thus, the senescence response may be antagonistically pleiotropic, promoting early-life survival by curtailing the development of cancer but eventually limiting longevity as dysfunctional senescent cells accumulate.
PMID: 15734683 [PubMed - indexed for MEDLINE]
Edited by zoolander, 12 December 2006 - 05:50 PM.
Posted 13 December 2006 - 12:10 PM
The relevance to allotopic expression is that cell-cell mitochondrial donation is actually possible. That is the practical significance of the study I cited. It means that a natural system of mitochondrial transfer already exists and can be exploited to deliver healthy mitochondria to rescue mitochondrially dysfunctional cells.I cannot see how the article you presented does have any relevance to allotopic expression.
Sure, but I'm not seeing the point you are making. Can you explain?Note that
a) mitotic cells were used, whose mitochondrial depletion by ethidium bromide hardly reflects the low abundance of mitochondrial damage in these tissues in vivo and that
Firstly, the notion that clonal expansion favors faulty mitochodria, which is what I believe you're implying, is theoretical. Secondly, even if it were proven to be true, it is easier to target faulty mitochodria for phagocytosis and then replenish them using this method than it is to solve the AE problem. Thirdly, we don't know how a cell would respond if it were provided with fresh and healthy mitochondria, therefore to assume that faulty clonal expansion would persist is unfounded. Also, AE does not address the problem of the aging brain but this approach does. It is a most remarkable discovery.b) even if this were the case there remains the fact that clonally expanded mitochondria have a replicative advantage compared to wild-type ones, which will lead to another clonal expansion, rapidly undoing the restauration of mitochondrial function.
Posted 13 December 2006 - 04:06 PM
Posted 13 December 2006 - 10:57 PM
You're saying because the experimental conditions where cell-cell mitochondrial donation was observed to work do not reflect normal physiology that it diminishes the potential therapeutic potential of this discovery. I disagree. The fact that such a mechanism of such complexity exists in first place, ie that mitochondria can be transferred from cell to cell (with all the specialized processes required to make that happen) has enormous implications since not only does it provide a mechanism which could be exploited for such transfer to take place therapeutically but it also suggests that mutated mitochondria could "infect" other cells and therefore allow other strategies of dealing with mitochondrial dsiease to be explored.In vivo, mitotic cells show less mitochondrial damage than postmitotic ones. Adding ethidium bromide fully depletes the cell?s mitochondria - mitotic cells in the body never come in this situation, not even mitochondria of postmitotic cells are 100% damaged, so I?m afraid this is not a model that exactly reflects the situation in the body.
Posted 16 December 2006 - 11:48 AM
Posted 16 December 2006 - 06:28 PM
mitochondria do take up electron in the form of NADH and FADH2 , for example via the malate-aspartate shuttle and the glycerophosphate shuttle.
To be clear, electrons are mainly produced in two metabolic pathways: the glycolysis and the TCA or Krebs cycle. The latter is located within the mitochondrial matrix; the glycolysis is located in the cytosol, therefore its electrons must be imported into the mitochondria.
Your idea concerning extracellular antioxidants is good in theory, and there is some evidence that most electrons in the extracellular space are taken up by ascorbic acid; but then, how do you explain the lack of increase in maximum lifespan even at very high doses of applied antioxidants?
Posted 16 December 2006 - 08:54 PM
Posted 03 January 2007 - 01:08 PM
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